A Phase II Trial of Ridaforolimus and Exemestane, Compared to Ridaforolimus, Dalotuzumab and Exemestane in Participants With Breast Cancer (MK-8669-064)

NCT01605396 | Completed Phase 2 Results

• 3 other identifiers: 8669-0642012-000335-11MK-8669-064
• Study Type: interventional
• Target: 80
• Locations: 0 countries
• Sites: N/A

Brief Summary

The purpose of the study is to evaluate the efficacy of the triplet of ridaforolimus, dalotuzumab and exemestane compared to the combination of ridaforolimus and exemestane in post-menopausal participants with breast cancer. The primary hypothesis of the study is that the triplet of ridaforolimus, dalotuzumab and exemestane will improve progression free survival (PFS) compared to ridaforolimus and exemestane.

Conditions

Breast Neoplasms

Outcome Measures

Primary Outcomes (1)

• 1. Progression-free Survival (PFS) According to Response Criteria in Solid Tumors Version 1.1 (RECIST 1.1) Based on Blinded Independent Central Review (BICR)

  PFS was defined as the time from randomization to progressive disease, or death, whichever occurs first. Response was assessed according to RECIST 1.1 by BICR. According to RECIST 1.1, progressive disease (PD) was defined as a 20% relative increase in the sum of diameters (SOD) of target lesions, taking as reference the nadir SOD and an absolute increase of \>5 mm in the SOD, or the appearance of new lesions. PFS was analyzed using the Kaplan-Meier method and median PFS (95% confidence interval \[CI\]) in weeks was reported for each treatment arm. Per protocol, participants remained on assigned treatment until disease progression. Participants who discontinued study treatment for reasons other than disease progression continued to be assessed by imaging until objective documentation of progression. All participants (including participants who discontinued study treatment) were followed for survival until investigator notification to discontinue.

  From Day 1 through last post-study efficacy follow-up (up to ~19 months)

Secondary Outcomes (3)

• Percent Change From Baseline in Sum of Target Lesion Diameters at Week 16

  Baseline, Week 16

• 3. Percentage of Participants With Objective Response (Objective Response Rate [ORR]) According to Response Criteria in Solid Tumors Version 1.1 (RECIST 1.1) Based on Blinded Independent Central Review (BICR).

  From Day 1 through last post-study efficacy follow-up (up to ~19 months)

• Overall Survival (OS)

  From Day 1 through last post-study efficacy follow-up (up to ~19 months)

Study Arms (2)

Ridaforolimus + Dalotuzumab + Exemestane

EXPERIMENTAL

Participants receive ridaforolimus 10 mg orally (PO) every 5 days (QD x 5) plus dalotuzumab 10 mg/kg intravenously (IV) every week (QW) plus exemestane 25 mg PO every day (QD) in 28-day cycles until documented disease progression or unacceptable toxicity.

Drug: Ridaforolimus; Drug: Dalotuzumab; Drug: Exemestane

Ridaforolimus + Exemestane

ACTIVE COMPARATOR

Participants receive ridaforolimus 30 mg PO QD x 5 plus exemestane 25 mg PO QD treatment in 28-day cycles until documented disease progression or unacceptable toxicity.

Drug: Ridaforolimus; Drug: Exemestane

Interventions

Ridaforolimus DRUG

Ridaforolimus 10 mg tablet, administered PO at a dose of 10 mg (triplet) or 30 mg (doublet) depending upon randomization, on Days 1-5, 8-12, 15-19, \& 22-26 of 28-day cycle.

Also known as: MK-8669, AP23573

Ridaforolimus + Dalotuzumab + Exemestane; Ridaforolimus + Exemestane

Dalotuzumab DRUG

Dalotuzumab administered 10 mg/kg IV weekly on Days 1, 8, 15, and 22 of 28-day cycle.

Also known as: MK-0646, h7C10

Ridaforolimus + Dalotuzumab + Exemestane

Exemestane DRUG

Exemestane 25 mg tablet administered PO QD.

Also known as: Aromasin

Ridaforolimus + Dalotuzumab + Exemestane; Ridaforolimus + Exemestane

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Females with a histologically confirmed diagnosis of breast cancer that is metastatic or locally advanced (locally advanced tumors must not be amenable to
• surgery or radiation therapy with curative intent) with the following pathological characteristics determined locally: estrogen receptor positive and Human Epidermal Growth Factor Receptor 2 (HER-2) negative, and Ki67 (a tumor marker) ≥ 15% determined by the central study laboratory
• Post-menopausal
• With advanced breast cancer whose disease was refractory to previous letrozole or anastrozole
• Has at least one confirmed measurable metastatic lesion
• Has a performance status ≤ 1 on the Eastern Cooperative Oncology Group (ECOG) performance scale
• Has a life expectancy of at least 3 months
• Adequate organ function

You may not qualify if:

• Is receiving any other concurrent systemic tumor therapy, including
• hormonal agents and HER-2 inhibitors
• Previously received rapamycin or rapamycin analogs, including
• ridaforolimus, temsirolimus, or everolimus
• Received prior treatment with Insulin-like Growth Factor 1 Receptor (IGF-1R) inhibitors, Phosphatidylinositol 3-Kinase (PI3K) inhibitors, or
• other experimental agents that target PI3K, Protein Kinase B (AKT), or Mammalian Target of Rapamycin (mTOR) pathway
• Is receiving chronic corticosteroids administered at doses greater than
• those used for normal replacement therapy
• Has active brain metastasis or leptomeningeal carcinomatosis; patients
• with adequately treated brain metastases are eligible if they meet certain criteria
• Known allergy to macrolide antibiotics
• Has an active infection requiring antibiotics
• Significant or uncontrolled cardiovascular disease
• Poorly controlled Type 1 or 2 diabetes
• Is known to be Human Immunodeficiency Virus (HIV) positive

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Related Publications (1)

• Rugo HS, Tredan O, Ro J, Morales SM, Campone M, Musolino A, Afonso N, Ferreira M, Park KH, Cortes J, Tan AR, Blum JL, Eaton L, Gause CK, Wang Z, Im E, Mauro DJ, Jones MB, Denker A, Baselga J. A randomized phase II trial of ridaforolimus, dalotuzumab, and exemestane compared with ridaforolimus and exemestane in patients with advanced breast cancer. Breast Cancer Res Treat. 2017 Oct;165(3):601-609. doi: 10.1007/s10549-017-4375-5. Epub 2017 Jul 5.

  PMID: 28681171 RESULT

MeSH Terms

Conditions

Breast Neoplasms

Interventions

ridaforolimus; dalotuzumab; exemestane

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme Corp.

ClinicalTrialsDisclosure@merck.com

1-800-672-6372

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 22, 2012
• First Posted: May 24, 2012
• Study Start: July 4, 2012
• Primary Completion: February 19, 2014
• Study Completion: March 15, 2018
• Last Updated: March 25, 2019
• Results First Posted: March 25, 2019

Record last verified: 2019-03

Data Sharing

• IPD Sharing: Will share